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Viral vector–delivered gene-editing tool to excise HIV in mice

Posted July 12, 2017

Researchers reported in May they had used virus-delivered gene edits to eliminate HIV reservoirs within cells of mice.

The study results (Mol Ther 2017;25:1168-1186) indicate the methods were effective in three groups of mice: one group with inactivated HIV, another acutely infected with EcoHIV—the mouse equivalent of HIV—and a third group that had humanized bone marrow, liver, and thymus cells and was inoculated with HIV to create chronic infections. The study used an adeno-associated virus vector to deliver multiplex single-guide RNAs plus Staphylococcus aureus Cas9 into infected cells and excise the HIV genomes.

The researchers were affiliated with Temple University in Philadelphia, the University of Pittsburgh, and Sichuan University in Chengdu, China.

The study authors note that retroviral therapy suppresses HIV replication, but the virus can hide within its host's cells and integrate its DNA into the cell's genome. Then, once therapy ends, the viral load surges. The researchers hope that using a vector to deliver gene-editing tools into the cells can eliminate the virus.

CRISPR-Cas9 gene editing is based on an adaptive immune system from bacteria that excises gene segments of viral predators.

An announcement from Temple University hails the study results as a major step toward curing HIV infection. One of the authors, Kamel Khalili, PhD, said in the announcement that further research should progress toward examining use in humans.

"The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells," Dr. Khalili said. "Our eventual goal is a trial in human patients."